BACKGROUND: There is an increased risk of specimen labeling errors with the generation of a high volume of pathology specimens. Measuring specimen labeling accuracy has been suggested as a possible measure for patient safety. OBJECTIVE: We sought to identify operational areas for improvement around specimen handling with the institution of a standardized specimen labeling protocol in the Duke University Medical Center Department of Dermatology. The average rates of specimen labeling events before and after implementation of this protocol were analyzed to determine the efficacy of this systematic approach. METHODS: We collected the monthly aggregated rates of specimen labeling events occurring with skin specimens processed through the Duke University Medical Center Department of Pathology from December 2008 through June 2011. The average monthly rates of events per 1000 cases for the time periods from December 2008 through March 2010 and June 2010 through September 2011 were compared. RESULTS: The data collected showed a statistically significant decline in the average monthly rate of specimen labeling errors after institution of the protocol. Before implementation, specimen labeling events occurred at a rate of 5.79 events per 1000 with a decrease to 3.53 events per 1000 after integration of this system (P = .028). LIMITATIONS: Limitations of this study include possible sampling error and regression toward the mean. CONCLUSIONS: Low-cost, process-driven interventions are effective in the reduction of specimen handling errors.